Phase 2
N=72
A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Itacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101)
B-Cell Malignancies
Bottom Line
View on ClinicalTrials.gov: NCT02018861 ↗Enrolled (actual)
72
Serious AEs
40.9%
Results posted
Jun 2022
Primary outcome: Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) — 1; 3; 3; 32 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Parsaclisib (Drug); Itacitinib (Drug); Rituximab (Drug); Ifosfamide (Drug); Carboplatin (Drug); Etoposide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Incyte Corporation
- Primary completion
- Apr 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
1; 3; 3; 32; 25; 4 | — |
| SECONDARY Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants |
0.0; 0.0; 66.7; 0.0 | — |
| SECONDARY Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL |
100.0 | — |
| SECONDARY Part 6: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL |
— | — |
| SECONDARY Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM |
100.0 | — |
| SECONDARY Part 2: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM |
— | — |
| SECONDARY Part 6: ORR Based on the VIth International Workshop on WM Response Assessment for Participants With WM |
— | — |
| SECONDARY Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT |
0.0; 0.0; 50.0; 36.4; 16.7; 50.0 | — |
| SECONDARY Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT |
0.0; 0.0; 0.0; 100.0; 50.0 | — |
| SECONDARY Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT |
50.0; 100.0 | — |
| SECONDARY Cmax of Itacitinib in Combination With Parsaclisib |
887 | — |
| SECONDARY Tmax of Itacitinib in Combination With Parsaclisib |
2.0 | — |
| SECONDARY Cmin of Itacitinib in Combination With Parsaclisib |
32.8 | — |
| SECONDARY AUC0-t of Itacitinib in Combination With Parsaclisib |
6450 | — |
| SECONDARY AUC0-τ of Itacitinib in Combination With Parsaclisib |
6450 | — |
| SECONDARY Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib |
354; 791; 808; 1270; 3270; 4010 | — |
| SECONDARY Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib |
2.0; 1.0; 1.0; 1.0; 0.5; 1.0 | — |
| SECONDARY Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib |
127; 104; 156; 178; 295; 864 | — |
| SECONDARY Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib |
2110; 3260; 3730; 5990; 13300; 16800 | — |
| SECONDARY Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib |
7130; 6910; 11100; 11900; 24800; 47700 | — |
| SECONDARY Part 3: Cmax of Parsaclisib Monotherapy |
1550; 2350; 1720; 2390; 1200; 1720 | — |
| SECONDARY Part 3: Tmax of Parsaclisib Monotherapy |
0.5; 1.0; 1.0; 1.0; 2.0; 1.5 | — |
| SECONDARY Part 3: Cmin of Parsaclisib Monotherapy |
214; 281; 395; 296; 197; 477 | — |
| SECONDARY Part 3: AUC0-t of Parsaclisib Monotherapy |
6530; 10700; 7010; 8430; 7110; 12000 | — |
| SECONDARY Part 3: AUC0-τ of Parsaclisib Monotherapy |
12600; 19500; 17900; 20100; 14200; 28000 | — |
Summary
Open-label, dose-escalation study in subjects with previously treated B-cell malignancies to find maximum tolerated dose (MTD) or pharmacologic active dose of a PI3Kδ inhibitor, parsaclisib, as monotherapy and in combination with: itacitinib (INCB039110), a JAK1 inhibitor; rituximab; and rituximab, ifosfamide, carboplatin, and etoposide. Parsaclisib inhibits PI3Kδ, a protein involved in growth and survival of B-cell cancer cells.
Eligibility Criteria
Inclusion Criteria
- Aged 18 years or older, with lymphoid malignancies of B-cell origin including:
- Indolent / aggressive B-cell non-Hodgkin's lymphoma (NHL)
- EXCLUDING: Burkitt's lymphoma and precursor B lymphoblastic leukemia/lymphoma
- INCLUDING: any non-Hodgkin's B cell malignancy such as chronic lymphocytic leukemia (CLL) and rare non-Hodgkin's B- cell subtypes such as hairy cell leukemia, Waldenström macroglobulinemia (WM), mantle cell leukemia (MCL), and transformed NHL histologies
- Hodgkin's lymphoma (HL)
- Life expectancy of 12 weeks or longer
- Subject must have received ≥ 1 prior treatment regimen(s)
- The subject must not be a candidate for potentially curative therapy including hematopoietic stem cell transplantation, except where one of the standard therapy regimen combinations may be used prior to transplantation per standard medical practice
Exclusion Criteria
- Has history of brain metastasis, spinal cord compression (unless treated, asymptomatic, and stable on most recent imaging and enrolling in expansion cohort), or lymphoma involving the central nervous system (CNS)
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 3 (≥ 2 during dose escalation)
- Received allogeneic hematopoietic stem cell transplant within the last 6 months, or has active graft versus host disease (GVHD) following allogeneic transplant, or currently receiving immunosuppressive therapy following allogeneic transplant
- Received autologous hematopoietic stem cell transplant within the last 3 months
- Inadequate marrow reserve assessed by hematologic laboratory parameters
- Inadequate renal or liver function
- Known HIV infection, or hepatitis B virus (HBV) or hepatitis C virus (HCV) viremia or at risk for HBV reactivation
Data sourced from ClinicalTrials.gov (NCT02018861). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.